Synthesis , characterization and antibacterial activity of new series of sulfamethoxazole derivatives

109 Pages·2015·3.09 MB·English

Republic of Iraq
Ministry of Higher Education
and Scientific Research
University of Al-Mustansiriyah
College of Pharmacy

Synthesis , characterization and antibacterial activity of
new series of sulfamethoxazole derivatives

A Thesis
Submitted to the Department of Pharmaceutical Chemistry and the Committee of Graduate
Studies of the College of Pharmacy-University of Al-Mustansiriyah in Partial Fulfillment of
the Requirement for the Degree of Master in Pharmacy “Pharmaceutical Chemistry”
By
Zainb Mohammed abd al-khaliq
(B.Sc. Pharmacy 2012)
Supervised by
Assist. Prof. Assist. Prof.
Dr. Monther Faisal Mahdi Dr. Rafah Al-Smaism

2015 AD 1436 AH
Certification
We certify that this thesis, “Synthesis , characterization and antibacterial
activity of new series of sulfamethoxazole derivatives”, was prepared under our
supervision at the Department of pharmaceutical Chemistry, College of Pharmacy-
University of AL-Mustansiriyah as a partial fulfillment of the requirements for the
degree of Master in Pharmacy (Pharmaceutical chemistry).
Signature:
Name: Assist. Prof. Dr. Monther Faisal Mahdi
Address: Department of Pharmaceutical Chemistry
College of Pharmacy-University of Al-Mustansiriyah
Date: / /2015

Signature:
Name: Assist. Prof. Dr. Rafah Al-Smaism
Address: Department of Pharmaceutical Chemistry
College of Pharmacy- University of Al-Mustansiriyah
Date: / /2015

In view of the available recommendation, we forward this thesis for debate by
examination committee.
Signature:
Name: Dr.Inam S.Arif
Chairman of the Committee of Graduate Studies in the College of Pharmacy
Date: / /2015
Certification
We, the examining Committee after reading this thesis, “Synthesis ,
characterization and antibacterial activity of new series of sulfamethoxazole
derivatives”, and examining the student Zainb Mohammed abd al-khaliq in its
contents, find it adequate as a Partial Fulfillment of the requirements for the
Degree of Master in Pharmacy (Pharmaceutical Chemistry).

Signature:
Name:
(Chairman)
Date: / /2015

Signature: Signature:
Name: Name:
(Member) (Member)
Date: / /2015 Date: / /2015

Approved for the University Committee for the Graduate Studies.
Signature:
Name: Assistant. Prof. Dr. Monther Faisal Mahdi
Dean of College of Pharmacy
University of Al- Mustansiriyah
Date: / /2015
﴾ ﻼﻴِﻠَﻗ ﱠﻻِإ ﻢِ ﻠْﻌِْﻟا ﻦﻣِ ﻢﺘﻴِﺗوُأ ﺎﻣو ﴿
ً ْ ْ ُ َ َ

ِ ِ
ﻢﻴﻈﻌﻟا ﻲﻠﻌْﻟا ﷲا قَ ﺪﺻ
َ ﱡ َ َ

٨٥ ﺔﻳﻵا/ءاﺮﺳﻹاةرﻮﺳ
Dedication

TO

Those Who Live With Me Day And Night…..

The Spirit Of My Father…

The Loving Heart Of My Mother...

The Pride Of My Life...

My Elder Brother , Zaid ;
My Teachers…
My Friends…
Sisters And Brothers
With My Love

Zainb Mohammed abd al-khaliq

I
Acknowledgments

Praise is to almighty Allah gracious for enabling me to finish
what I started and for helping me to present this work.
I would like to express appreciation to my supervisor and my
Idol Assist. Prof. Dr. Monther Faisal Mahdi for providing unlimited
support, valuable suggestions, scientific guidance and for his
magnificent advices throughout my work.
I would like to express my heartfelt gratitude and appreciation
to my supervisor Assist. Prof. Dr. Rafah Al-Smaism for her valuable
advices, guidance, support and help in passing all the obstacles
throughout my work and for being the one who learned me how to be
a professional chemist and skillful worker.
My deepest thanks with respect to Teacher Dr. Inam S. Arif, for
her encouragement.
My deepest thanks with respect to Assist. Prof. Dr. Ashour H.
Dawood, for his support and all the valuable advices and support.
My deepest thanks with respect to Assist. Prof. Dr. Ayad
Mohamed Rasheed, for his scientific advices and support throughout
my wok.
Special thanks to Dr. Abdul Rasool M.Wayyes, for their help
throughout my work.
I would like to express my deep gratitude to Dr.Mahmood
Jawad Abu-Al-Shaeer ,AL-Rafidain University dean of the Faculty,
for offering the opportunity to continue my postgraduate study.
II
I am honestly grateful to Mrs. Hala Ayad for her constant help
and for her great support through the course of this work.
Special thanks for Zina Alaa, Zina Hussien, Amani Sabri,
Asmaa Jasim for all the help during my work .
Special thanks for Dr. Suhad Faisal Hatem for all the help
during my work .
Special thanks for Dr.Sajid Al Khalidy(consultant
Immunology), Dr.Firas H. Qanbar, Ass.prof. Mohammed Ayad
Abbas, Biologist Haider majeed, Bacteriologist lubna M. AL-Taie
,Biologist Rawaa Asad Salman ,Dr. Sahar Al-Juboori, for all the
help during my work.
Special thanks for Prof. Dr. Saad M Shuker Al-Mashhdani for
all the help during my work.
Special thanks for Dr. Thaer Arhiyl Al-Bajjari for all the help
during my work
Finally, I would like to express my deep gratitude to all kind,
helpful, and lovely people who helped me directly or indirectly to
complete this work.

Zainb Mohammed abd al-khaliq

III
Contents Page
I
Dedication
II
Acknowledgment
IV
List of Contents
VIII
List of Tables
IX
List of Schemes
IX
List of Figures
X
List of Abbreviations
XII
Abstract
Chapter one: Introduction

1.1 Background of Antibacterial agents 1

1.1.1 Mechanisms of action of antibacterial agents 2
1.1.2 Bacterial antimicrobial resistance 3
1.2 introduction of the sulfa drugs 4
1.2.1 Structural activity relationship of sulfonamides 7
1.2.2. Sulfamethoxazole 10
IV
1.3.Schiff bases 11
1.4. Heterocyclic compounds 12
1.5. Thiazolidinone 16
1.6.Biological Activities of 4-thiazolidinones 16
1.6.1 . Antiviral Activity 16
1.6.2. Anticonvulsant and Antidepressant Activity 17
1.6.3. Antitubercular Activity 18
1.6.4. Anticancer Activity 18
1.6.5.Antibacterial 19
Activity
1.6.6. Antifungal Activity 19
1.6.7. Anti-inflammatory and Analgesic Activity 20
1.7. Chalcone 22
1.7.1.Non Biological importance of chalcones 22
1.7.2. Biological importance 23
1.8. New analogues of antibiotics 23
26
1.9. Aim of work

V
Chapter two: Experimental work
2.1 Chemicals and Equipments 27
2.1.1 Chemicals 27
2.1.2 Equipments 29
2.2 Methods of characterization and identifications 29
2.2.1 Thin layer chromatography (TLC) 29
2.2.2 Melting points 30
2.2.3 Infrared spectra 30
2.2.4 Elemental Microanalysis 30
2.2.5 Proton Nuclear Magnetic Resonance ( 1H -NMR 30
2.3 Chemical synthesis 30
2.3.1 Chemical Synthesis of Schiff base [ 4-((4- 30
methoxybenzylidene)amino)-N-(5-methylisoxazol-3-
yl)benzenesulfonamide] (M )
1
2.3.2 Synthesis of 4-(2-(4-methoxyphenyl)-4-oxothiazolidin-3-yl)- 31
N-(5-methylisoxazol-3-yl)benzenesulfonamide (M ).
2
2.3.3 Synthesis of (M ) 31
3a-f
2.4. Biological Activity 34
2.4.1. Antimicrobial Activity 34
2.4.2. Sensitivity Assay 34
VI